Encephalitis, Mild Encephalitis, Neuroprogression, or Encephalopathy—Not Merely a Question of Terminology

Abstract

Background: Psychoneuroimmunology research has presented emerging evidence of the involvement of inflammatory and immune mechanisms in the pathogenesis of severe mental disorders. In this context, new terms with increasing clinical relevance have been proposed, challenging the existing terms, and requiring consensus definitions of the new ones.Method: From a perspective of longstanding personal involvement in clinical settings and research in psychoneuroimmunology, the new and the existing terms are critically reconsidered.Results: Meningoencephalitis and encephalitis are comparably well defined clinical terms in neuropsychiatry, although in the individual case approach diagnosis can be difficult, for example in some cases of encephalitis that are described with normal cerebrospinal fluid findings, or often in chronic encephalitis. Encephalopathy is also a widely accepted term, however, with a surprisingly broad meaning with regard to the assigned underlying pathophysiology, ranging from one-hit traumatic encephalopathy to inflammatory encephalopathy, the latter term addressing a type of brain dysfunction secondary to acute systemic inflammation without proven brain autochthonus inflammation (neuroinflammation). However, this latter assumption and term may be wrong as neuroinflammation is difficult to prove in vivo. With emerging insights into prevailing inflammatory and neuroinflammatory mechanisms that are involved in the pathogenesis of severe mental disorders, the interdependent aspects of sensitive assessment and potential clinical relevance of mild neuroinflammation are becoming more apparent and of increasing clinical interest. The new terms “mild encephalitis,” “parainflammation,” and “neuroprogression” show considerable overlap in addition to gaps and hardly defined borders. However, details are hard to discuss as available studies use many biomarkers, but most of these are done without an established categorical attribution to exclusive terms. Most important, the three new concepts (neruoprogression, parainflammation, and mild encephalitis) are not mutually exclusive, even at the individual case level, and therefore will require state-related individual assessment approaches beyond large confirmatory studies.Conclusion: The newly proposed terms of mild encephalitis, parainflammation, and neuroprogression have an emerging clinical relevance, but respective borders, gaps and overlap in between them remain unclear, and these concepts may even be seen as complementary. Categorical delineation of the new and reconsideration of the existing terms with respect to individualized psychiatric treatment is required for better clinical use, eventually requiring a consensus approach. Here, a critique based on available data and a focus on clinical perspective was outlined, which may help to enhance fruitful discussion. The idea followed here is in line with pillar number six as proposed for the Research Diagnostic Domains, i.e., to provide and follow new concepts in psychiatric research.

Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations

“…The recommendations worked out here for Abs assessment and respective diagnostic and therapeutic consequences in schizophreniform psychoses were based on consensus from emerging clinical evidence rather than from systematic randomized studies as is the case with the present recommendations for diagnosis and treatment of AE [31]. Beyond, it should be recognized that indeed both well-established clinical terms (like encephalitis, encephalopathy, neuroinflammation) and newly proposed terms (such as AP, AE) are hardly exactly defined, thus for clinical use typically represent just clinical case definitions based on respective Table 3 The most important known autoantibodies that can be associated with symptoms of schizophreniform psychoses [9,15,31,34,36,37,38,48,63,71,79,81,82,84,85,90 limited and steadily emerging clinical consensus [6,12]. In addition, the possibility of underlying so far not identified new Abs is also limiting the whole issue.…”

“…Since then, a large number of other antineuronal Abs against cell surface antigens and their associated syndromes have been identified [ 15 , 17 , 31 , 89 , 90 ]. Because these syndromes can be accompanied by polymorphic psychotic symptoms, immunological concepts of schizophreniform psychoses have gained considerable attention since [ 1 , 6 , 15 , 22 , 36 , 67 , 68 , 76 , 77 , 78 , 84 ]. In a German case series of 100 patients with different forms of AEs with Abs against antineuronal antigens, over half of the patients (60%) presented with psychotic symptoms [ 36 ].…”

Case report of the treatment and experience of mental disorders due to chronic viral encephalitis

“… 7 However, the early presentation of disturbance of consciousness in some patients cannot be readily recognised; in addition, the prominent mental symptoms cover up other symptoms of VE. 8 …”

Psychiatric Presentation of Anti-NMDA Receptor Encephalitis

“…The FDG-PET finding probably does not reflect classic neuroinflammation, so it may be better to speak of encephalopathy rather than encephalitis in such cases [cf. (8, 26)].…”